The modern era of antiplatelet therapy was founded by large clinical trials demonstrating the benefit of aspirin and clopidogrel in the treatment and prevention of acute coronary syndromes. The concept of antiplatelet drug "resistance" emerged during the 1990s with studies revealing considerable residual platelet aggregation in some patients despite aspirin treatment. In the wake of these reports, larger studies established an association between high on-treatment platelet reactivity and thrombotic events. The possible mechanisms explaining this phenomenon are manifold and reflect the complexity of platelet function, thrombus formation and cardiovascular disease. Some mechanisms apply to both drugs, while others apply only to one of them. In recent years, efforts have been made to translate this information into an improved clinical outcome by modifying antiplatelet drug regimens. Several studies investigated measurements of on-treatment platelet reactivity, but large clinical trials have failed to demonstrate substantial clinical benefit of individually tailored antiplatelet therapy according to platelet function tests. This article provides an integrated review of interindividual variability in the efficacy of aspirin and clopidogrel with particular emphasis on possible effect-modifying mechanisms and clinical implications.
BackgroundAspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported.AimTo investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients.MethodsWe performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B2.ResultsPlatelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml).ConclusionPlatelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.
Almost one third of the seropositive children had HZ during primary chemotherapy. Of those treated on high risk protocols more than half had one or more eruptions during the course of treatment. The risk of complicated HZ is small, but prolonged intensive chemotherapy can lead to considerable morbidity from repeated eruptions. Attempts to improve immunity by vaccination after attaining remission seem warranted.
Rapid evaluation of platelet function may be advantageous in the setting of surgical and interventional procedures to tailor treatment of ongoing bleeding. We investigated if platelet function testing performed with the Multiplate® Analyzer (Roche Diagnostics, Mannheim, Germany) only 5 minutes after blood sampling yields reliable test results compared to analyses performed 30 minutes after sampling as currently recommended. We included 48 patients with type II diabetes and stable coronary artery disease treated with aspirin 75 mg daily and 50 healthy individuals not taking any medications. Platelet aggregometry by the Multiplate® Analyzer was performed 5 and 30 minutes after blood sampling using arachidonic acid (1.0 mM), collagen (3.2 µg/ml) and adenosine diphosphate (ADP; 6.5 µM) as agonists. Compliance with aspirin was verified by serum thromboxane B2 measurements. Aggregation levels assessed 5 minutes after blood sampling correlated strongly with those assessed after 30 minutes irrespective of the agonist used (r-values 0.75-0.89, p values <0.0001). Aggregation levels were 4-8% lower and displayed a larger standard deviation when measured 5 minutes after sampling, compared to 30 minutes after sampling. Weak, but significant correlations were observed between platelet aggregation and platelet count (r-values = 0.28-0.39; p values <0.01). The currently recommended 30-minute standing time can be omitted, when platelet aggregation is measured using the Multiplate® Analyzer. Platelet aggregation measured 5 minutes after blood sampling correlates strongly with aggregation measured 30 minutes after sampling, but yields slightly lower aggregation levels. The Multiplate® Analyzer enables rapid on-site evaluation of platelet function.
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